Future Projections in Thyroid Eye Disease

Background: The thyroid eye disease (TED) treatment landscape is rapidly evolving. How new treatment options have impacted practice is unknown. Methods: We conducted a cross-sectional electronic survey of American and European Thyroid Association members between June 2 and June 30, 2021. The survey included TED questions about resources for its management, index cases for different severities and presentations of TED, barriers for the management of TED, and participants' concerns about TED. We classified respondents into three geographic categories: North America, Europe, or other regions. Results: Two hundred fifty-two eligible participants started the survey (15% response rate), and 227 completed it. Participants were mostly men (50.2%, 114/227), white (79.7%, 181/227), endocrinologists with a thyroid focus (66.1%, 150/227), practicing in a tertiary academic center (46.7%, 106/227), caring for 10 or more TED patients over the last 12 months (40.5%, 92/227), and reported not having a multidisciplinary TED clinic in their institution (52.8%, 120/227). The majority reported that new TED cases per annum have not changed in the past 10 years (47.5%, 108/227), and that TED patients are found in practice during the management of hyperthyroidism (41.8%, 95/227). For mild active TED, participants from Europe reported a higher use of selenium (73%[96/132] vs. 32%[20/62] of respondents from North America and 24%[8/33] of respondents from other regions). For moderate-to-severe active TED, there was a modest preference for teprotumumab as first-line therapy (37%, 23/62) among North American participants and intravenous (IV) steroids (73%[96/132], and 42%[14/33]) for participants from Europe and other regions, respectively. These treatment preferences did not change in patients with moderate-to-severe active TED with poorly controlled diabetes. In contrast, participants from the three geographic categories preferred IV steroids for optic neuropathy and women planning pregnancy. The three top "very important" concerns about TED management according to participants were: the cost of TED treatment (31.3%, 71/227), lack of effective TED treatments (19.8%, 45/227), and difficulty in predicting whether TED will develop (18.9%, 43/227). Conclusions: There is a marked geographic practice variation in the management of TED. Clinicians' concerns about TED management demand ongoing research on more effective treatment, TED predictive tools, and policy changes to improve the affordability of new TED therapies.

Introduction: Thyroid Eye Disease (TED) is an autoimmune inflammatory disease of the orbit that affects orbital fat, extraocular muscles, periocular tissue and lacrimal glands. TED activity can be assessed with a Clinical Activity Score (CAS) to identify active or inactive TED conditions. Dry Eye Diseases (DED) is one of the manifestations in patients with TED with a prevalence that varies from 27%-96%. The Asia Dry Eye Society (ADES) 2017 proposed a new concept for DED diagnosis and therapy, namely Tear Film Oriented Diagnosis (TFOD) and Tear Film Oriented Diagnosis Therapy (TFOT) with Tear Film Breakup Pattern (TBUP) examination. TBUP examination help in determine specific management of DED. The aim of this study is to determine the differences in TBUP in TED patients based on active and inactive. Methods: This is an analytical observational study with a cross-sectional design. The subjects were TED patients who came to the Cicendo Eye Hospital and met the inclusion criteria. The study was conducted at the National Eye Center of Cicendo Eye Hospital in April - June 2022. The data were analysed with the Chi-Square Test. Result: This study was conducted on 23 patients or 46 eyes. This study found a statistically significant differences in TBUP features in active and inactive TED patients (p=0.0001). The most common features of TBUP was found in active TEDs was dimples (55%). Conclusion: There are differences of TBUP features in active and inactive TED patient.

Risk Factors of Thyroid Eye Disease

Background/Aim. To evaluate the efficacy of methotrexate for the treatment of thyroid eye disease (TED). Methods. 36 consecutive patients with active TED, previously treated with corticosteroids but stopped due to the occurrence of side effects, were commenced on methotrexate therapy. Two different weekly doses were administered depending on the weight of the patient (7.5 mg or 10 mg). Clinical activity score (7-CAS), visual acuity (VA), ocular motility, exophthalmos, and eyelid position were retrospectively evaluated at 3, 6, and 12 months and compared with baseline data. Results. There was a statistically significant improvement in 7-CAS at 3, 6, and 12 months after treatment (P < 0.0001). There was no significant change in visual acuity. Ocular motility disturbances improved at 6 and 12 months (P < 0.001). There was no significant change in exophthalmos (mean 24 mm, SD 3 mm) or eyelid position (marginal reflex distance mean 6 mm, SD 1.5 mm) during the follow-up period. No side effects were registered. Conclusions. Methotrexate therapy is effective in reducing CAS and ocular motility disturbances. No significant improvement in proptosis or eyelid retraction should be expected from this treatment. Eventually, it might be considered a suitable alternative treatment in TED for patients who cannot tolerate steroids.

PurposeTo investigate the molecular pathways that drive thyroid stimulating hormone receptor (TSHR)–induced cellular proliferation in orbital fibroblasts (OFs) from thyroid eye disease (TED) patients.MethodsOrbital fibroblasts from TED and non-TED patients were treated with TSH and changes in gene expression and proliferation were measured. To determine the role of TSHR, TSHR-specific siRNA was used to deplete TSHR levels. Proliferation was measured by bromodeoxyuridine (BrdU) incorporation. PI3K/Akt activation was analyzed by Western blot. The PI3K inhibitor LY294002 was used to investigate PI3K/Akt signaling in OF proliferation. Expression of TSHR, inflammatory cytokines, proliferation related genes and miR-146a and miR-155 were measured by qPCR.ResultsOrbital fibroblasts from TED patients proliferate significantly more than non-TED OFs in response to TSH. TSH-induced proliferation was dependent upon TSHR expression and required the PI3K/Akt signaling cascade. TSHR activation stimulated miR-146a and miR-155 expression. TED OFs produced significantly more miR-146a and miR-155 than non-TED OFs. MiR-146a and miR-155 targets, ZNRF3 and PTEN, which both limit cell proliferation, were decreased in TSH treated OFs.ConclusionsThese data reveal that TSHR signaling in TED OFs stimulates proliferation directly through PI3K/Akt signaling and indirectly through induction of miR-146a and miR-155. MiR-146a and miR-155 enhance TED OF proliferation by reducing expression of target genes that normally block cell proliferation. TSHR-dependent expression of miR-146a and miR-155 may explain part of the fibroproliferative pathology observed in TED.

We previously presented evidence that TSH receptor (TSHR)-stimulating autoantibodies (TSAbs) bind to and activate TSHRs but do not bind to IGF1 receptors (IGF1Rs). Nevertheless, we showed that IGF1Rs were involved in thyroid eye disease (TED) pathogenesis because TSAbs activated crosstalk between TSHR and IGF1R. Teprotumumab, originally generated to inhibit IGF1 binding to IGF1R, was recently approved for the treatment of TED (Tepezza). To investigate the role of TSHR/IGF1R crosstalk in teprotumumab treatment of TED. We used orbital fibroblasts from patients with TED (TEDOFs) and measured stimulated hyaluronan (HA) secretion as a measure of orbital fibroblast activation by TED immunoglobulins (TED-Igs) and monoclonal TSAb M22. We previously showed that M22, which does not bind to IGF1R, stimulated HA in a biphasic dose-response with the higher potency phase dependent on TSHR/IGF1R crosstalk and the lower potency phase independent of IGF1R. Stimulation by TED-Igs and M22 was measured in the absence or presence of teprotumumab biosimilar (Tepro) or K1-70, an antibody that inhibits TSHR. We show: (1) Tepro dose-dependently inhibits stimulation by TED-Igs; (2) Tepro does not bind to TSHRs; (3) Tepro inhibits IGF1R-dependent M22-induced HA production, which is mediated by TSHR/IGF1R crosstalk, but not IGF1R-independent M22 stimulation; and (4) β-arrestin 1 knockdown, which blocks TSHR/IGF1R crosstalk and prevents Tepro inhibition of HA production by M22 and by a pool of TED-Igs. We conclude that Tepro inhibits HA production by TEDOFs by inhibiting TSHR/IGF1R crosstalk and suggest that inhibition of TSHR/IGF1R crosstalk is the mechanism of its action in treating TED.

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life.

PurposeThere is no universal consensus on second-line agents for the treatment of moderate/severe to sight-threatening thyroid eye disease (TED) to maintain remission after first-line intravenous methylprednisolone (IVMP). This study investigates the efficacy and safety of mycophenolate mofetil (MMF) in TED patients in a real-world setting and over a longer period than previous randomized controlled trials.MethodsA retrospective cohort study of TED patients with active moderate/severe to sight-threatening TED seen over a 4-year period. Data collected were visual acuity (VA), Clinical Activity Score (CAS), Gorman Diplopia scores, MMF dosing and side effects at 24, 52 and 78 weeks. Clinical efficacy was defined as an absence of relapse: no decline in best corrected LogMAR VA, no need for further steroids, no increase in CAS of ≥2.ResultsOut of 23 patients, 20 patients were included in this study. 10% (2/20) stopped MMF before 24 weeks. Median duration of MMF treatment was 76 weeks (1–140 weeks). 55% (11/20) had dysthyroid optic neuropathy (DON). In those with active moderate-severe TED without DON, clinical efficacy was seen in 100% (8/8) at 24 weeks, 87.5% (7/8) at 52 weeks, and 83.3% (5/6) at 78 weeks, with CAS decreasing from a baseline of 2.78±1.99 to 0.50±0.58 at 24 weeks, 0.50±0.82 at 52 weeks and 1.00±1.30 at 78 weeks. In DON, improvements were seen in 90% (9/10) at 24 weeks, 100% (7/7) at 52 weeks and 100% (4/4) at 78 weeks, with significantly reduced CAS scores from 2.55±1.54 to 0.83±1.27, 1.00±1.17 and 0.63±0.95 at 24, 52 and 78 weeks, respectively. Gorman score, VA and soft tissue inflammation parameters also improved throughout. There were two significant side effects over the treatment period.ConclusionMMF appears to be an effective and safe second-line immunosuppressive agent. Further studies aimed at elucidating optimal dosing regimens and ideal treatment duration will prove helpful.

Purpose:To evaluate the association between obstructive sleep apnea (OSA) and thyroid eye disease (TED) and its effect on disease activity.Methods:A prospective case–control study was conducted from January 2020 to March 2022. All TED patients (group A) were clinically evaluated. The activity of thyroid eye disease was calculated based on the clinical activity score (CAS), and grading of severity was done according to the EUGOGO classification. All TED patients (group A) were screened for OSA using the Snoring Tired Observed Pressure (STOP)-Bang survey. Age- and gender-matched control group patients (group B) without TED were screened for OSA.Results:One hundred TED patients and 138 control patients without TED were included in the respective groups. Sixty-two (62%) patients in group A and 48 (34.78%) patients in group B were having high risk of OSA, and this difference was statistically significant (P = 0.001). Further, in group A patients, on univariate analysis, TED activity was significantly associated with a high risk of OSA (P = 0.009). On multivariate logistic regression analysis, OSA also showed significant association with TED activity (odds ratio [OR]: 4.14, 95% confidence interval [CI]: 1.11-18.85 at 10% level; P = 0.05).Conclusion:Our study showed that OSA is significantly associated with TED disease and its activity. However, no significant association was found between OSA and severity of the disease.

BackgroundOccurrence of Graves’ disease (GD) has been reported following SARS-CoV-2 vaccine administration, but little is known about thyroid eye disease (TED) after SARS-CoV-2 vaccination.Case 1A 50-year-old non-smoker male was diagnosed with GD in March 2019 and treated with methimazole. In April 2020, he developed TED with bilateral proptosis, pain, erythema and diplopia and clinical activity score (CAS) 6/7. Following poor response to 3-month oral steroids, he underwent total thyroidectomy in November 2020. In six weeks, his TED improved (CAS 4/7) and thyroid stimulated immunoglobulin (TSI) levels normalized from 4.13 IU/l (preoperatively) to 0.70 IU/l (reference< 1.75 IU/l). In January 2021, he received 2 doses of the mRNA BNT162b2-SARS-CoV-2 vaccine (Pfizer-BioNTech). Three weeks after the second dose, TED deteriorated significantly with severe eye pain, lid swelling, conjunctival erythema, and worsening proptosis and diplopia (CAS 6/7). TSI levels rose to 4.45 IU/l, while patient was euthyroid on levothyroxine (TSH 2.3 mIU/l). He received 12 weekly methylprednisolone infusions (cumulative dose of 4.5 g) with limited response. He was then treated with three monthly cycles of intravenous tocilizumab with partial response (CAS 5/7).Case 2A 71-year-old non-smoker female had a 40-year history of hypothyroidism, controlled on levothyroxine. In March 2021, three days after her second dose of the mRNA-1273 SARS-CoV-2 vaccine (Moderna), she developed bilateral eye swelling and burning. She initially received anti-histamines and steroid eye drops without improvement. By August 2021, her eyes further deteriorated with eye pain, redness, lid edema and erythema, diplopia, and worsening proptosis (CAS 4/7). She also experienced 20 Ib weight loss, palpitations, tremors, and heat intolerance. TSI index was 5.5 (reference ≤1.3), TSH was undetectable, and FT4 1.4 ng/dl (reference 0.93-1.70 ng/dl). Levothyroxine was discontinued. Two weeks later she was admitted to the hospital with loss of color vision and decreased visual acuity in the right eye. She received 2 daily doses of 1 g intravenous methylprednisolone and intravenous teprotumumab on hospital day 3. She responded well to teprotumumab infusions every 3 weeks, with return of color vision and improvement of proptosis and periorbital edema (CAS 1/7).DiscussionActivation of TED has so far only been described in four patients following SARS-CoV-2 vaccination. Here we report two more cases: one of TED deterioration in a GD patient with prior TED, and one of de novo TED progressing to dysthyroid optic neuropathy in a patient with a long history of Hashimoto's hypothyroidism. Possible etiologies include a maladaptive autoimmune/inflammatory syndrome from polyclonal B cell stimulation by adjuvants or activation of preexisting autoimmune disease. The possibility of new onset or deterioration of TED after SARS-CoV-2 vaccination in patients with underlying autoimmune thyroid disease and its mechanism should be further studied.Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:18 p.m. - 1:23 p.m.

To compare characteristics of unilateral vs. bilateral thyroid eye disease (TED). This retrospective analytical cross-sectional study was conducted on patients with TED who were evaluated at an academic referral center over a 6-year period. We compared demographics, activity (clinical activity score) and severity (EUGOGO classification) of TED, thyroid disease duration, TED duration, the time interval between thyroid and eye involvement, thyroid function status, and clinical signs between bilateral and unilateral TED. Three hundred eighty-three patients including 213 females (55.6%), who had a mean age of 40.23 ± 13.72years, were enrolled. Active TED was seen in 8.8% of bilateral and none of unilateral cases (P = 0.04). Bilateral TED patients had more severe disease (P = 0.001). The distribution of hyperthyroidism, hypothyroidism, and euthyroidism was significantly different between unilateral and bilateral groups (P = 0.001). Abnormal ocular motility was present in 26.3% versus 2.3% of bilateral and unilateral ones, respectively (P = 0.001). Proptosis was more prevalent in bilateral than unilateral cases (P = 0.001). We did not observe any statistically significant difference between the two groups in others variables. Bilateral TED patients present with more severity, activity, movement abnormality, proptosis, and hyperthyroidism.

Thyroid eye disease is a disabling autoimmune disease associated with orbital inflammation and tissue remodeling which can result in significant proptosis, leading to visual alterations and is potentially sight threatening. Current evidence indicates that autoantibodies to the insulin-like growth factor 1 receptor (IGF-1R), along with the thyroid-stimulating hormone receptor (TSHR), mediate the pathogenesis in susceptible individuals. Teprotumumab, a monoclonal IGF-1R antagonist, has demonstrated previously in a 24 week, randomized, controlled trial to produce significant changes in composite outcomes of proptosis and clinical activity score as compared with placebo. Further examination of the proptosis results reported here, indicate that the proptosis outcome (≥ 2 mm reduction) was met in 71.4% of the teprotumumab-treated patients as compared with 20% of the placebo-treated patients (p < 0.001). Additionally, the proptosis benefit was observed early in the trial (study week 6), and all individual patients demonstrated some benefit at week 24. Improvement was noted among smokers, non-smokers, men and women, and particularly those with higher levels of proptosis at baseline. The level of proptosis reduction with teprotumumab reported here is similar to that seen with decompression surgery. If these results are confirmed in the ongoing Phase 3 trial, teprotumumab will offer an alternative to surgery and its associated complications.

IntroductionThyroid eye disease (TED) is most often associated with Graves’ hyperthyroidism and bilateral involvement, whereas presentation with hypothyroidism or as a unilateral process is uncommon. Even more rarely, autoimmune hypothyroidism may evolve into Graves’ hyperthyroidism due to a shift in TSH receptor antibody (TRAb) activity.Clinical CaseA 48-year-old man with hypertension, dyslipidemia, and a current smoker was referred by an ophthalmologist for progressive right eye bulging, ocular pain, and redness. Examination revealed right-sided unilateral proptosis and lid retraction, with a Clinical Activity Score (CAS) of 5, consistent with active thyroid eye disease (TED) and severe disease according to the European Group on Graves’ Orbitopathy (EUGOGO) classification. Laboratory evaluation demonstrated overt hypothyroidism with strongly positive TPO and total TRAb antibodies. Thyroid ultrasound showed mild diffuse enlargement with heterogeneous echotexture, and orbital MRI confirmed hypertrophy of the right extraocular muscles (Figure 1). The patient received high-dose intravenous methylprednisolone (total 4.5 g over 12 weeks) and levothyroxine 50 μg/day. Smoking cessation was achieved. At follow-up, thyroid function initially improved, but TED remained active. Subsequently, while TED stabilized, the patient developed biochemical hyperthyroidism; levothyroxine was discontinued. On further follow up, overt hyperthyroidism was confirmed, and methimazole was initiated and titrated to 10 mg/day, resulting in biochemical stabilization and maintenance of stable TED without optic nerve involvement. At the last follow-up, the patient was maintained on carbimazole 10 mg/day with good clinical outcomes. Table 1 summarizes the follow-up stages of the patient. In fact, as we are in a resources-limited area, TRAb blocking and stimulating antibodies are not availableConclusionThis case highlights a rare presentation of severe unilateral TED initially associated with autoimmune hypothyroidism, later evolving into Graves’ hyperthyroidism. It emphasizes the importance of close biochemical monitoring, awareness of possible immune conversion, and multidisciplinary management to prevent sight-threatening complications, especially in high-risk patients such as smokers with elevated TRAb titers.Figure 1:CT scan of orbits showing extraoccular muscles enlargement Table 1:Patient follow up visits

Purpose Fatty infiltration of the extraocular muscles has been described radiographically in patients with thyroid eye disease (TED), yet it has not been studied on a large scale nor quantified. Our purpose was to define and characterize this entity in patients with TED. Methods An IRB-approved cross-sectional retrospective review of medical records identified patients with a clinical diagnosis of TED and at least one CT of the orbits. A 2:1 age and sex-matched control population consisted of patients without a history nor radiographic evidence of orbital disease or systemic thyroid abnormality. The presence of fatty infiltration in each extraocular rectus muscle was defined using Hounsfield units (HU). Laterality, muscles involved, and pattern of fatty infiltration were also evaluated. Student’s t-tests, Chi-square, and Fisher’s exact tests were used to compare TED and control groups. Results The study population consisted of 252 patients with TED and 504 age and sex-matched controls. Fatty infiltration was significantly more prevalent in TED patients (36/252, 14.3%) compared to controls (11/504, 2.2%) (p < .001). The mean density of fat infiltration was significantly lower in TED patients (−40.4 HU) than controls (−34.8 HU) (p = .048). In TED patients, the frequency of muscle involvement was inferior rectus (61.8%), lateral rectus (19.7%), superior rectus (11.8%) and medial rectus (6.6%), which was not significantly different than controls (p > .05). Most muscles (88.2%) in the TED group exhibited a heterogeneous pattern of infiltration, which did not differ from controls (p = .34). Conclusions This study characterizes fatty infiltration of the extraocular muscles in patients with TED.

IntroductionGraves’ Ophthalmopathy is an immune mediated inflammation in orbital and retroorbital tissues, occurs mainly with hyperthyroidism,10% with euthyroid and rarely with hypothyroidism, more frequently in females(1).Thyroid-stimulating hormone (TSH) receptor (TSHR) is the main auto-antigen, expressed in the thyroid gland, adipocytes and fibroblasts. It is aligned with insulin-like growth factor 1 (IGF-1) receptor. T cells activate TSHR and IGF-1 receptors and initiating a retro-orbital inflammation and accumulation of hydrophilic glycosaminoglycans (GAG)(2).Case46 yo, Hispanic obese male with history of type 2 DM and HLD, non-smoker, non- alcoholic, no illicit drugs. Family History of DM, no allergy,Home medications: Alogliptin benzoate 25mg/day, Metformin 1000mg twice/day and atorvastatin 10mg/day. Ophthalmology checkup 2 months before; visual acuity of 20/30, B/L nasal pterygium, no Diabetic retinopathy. Normal TSH (0.56ulU/ml) 6 months before. He presented to the Emergency department with 3 days of progressive redness, puffiness, photophobia and pressure like sensations in left eye, denied palpitations, change in bowel movements, weight loss/gain, heat/cold intolerance, fever, vomiting, headache, motor weakness, sensory loss. General examination alert, orientated x3,ABP 130/60, HR 75BPM, afebrile(98.4 F), BMI 37.56kg/m2, no tremors, no thyromegaly, normal heart, lung, abdomen examinations, no edema. Left eye conjunctival injection, proptosis, decrease visual acuity 20/60 and color vision, restricted eye movements, relative afferent pupillary defect, optic Neuropathy. Right eye nasal Pterygium and normal fundus examination. Laboratory findings; normal TSH 1.4ulU/ml, FT4 1.2ng/dl, FT3121ng/dl, High TSHR antibody4.69IU/L (normal less than 1.75IU/L), Thyroid peroxidase antibody 363IU/ml (normal less than 34.9IU/ml) and Thyroid stimulating immunoglobulin 3.55 IU/L (normal less than 0.55IU/L). Normal CBC, GFR, negative C-ANCA, P-ANCA antibodies. CT orbit showed marked exophthalmoses, prominence of infraorbital fat, thickening of inferior and medial rectus muscles of left eye. He was kept on IV Solumedrol 250mg Q 6hrs for 3 days, artificial tears. Symptoms improved, was discharged on tapering oral steroid starting with prednisone 80mg daily. Follow up after 5 days reported marked improvement of symptoms with slight proptosis, no optic neuropathy.ConclusionGraves’ Ophthalmopathy can occur in euthyroid patients. Presents mainly with bilateral eye affection, few cases have unilateral eye affection. IV or oral Steroid is the Main treatment of Graves’ ophthalmopathy with local eye measures and management of thyroid disease. Other options are teprotumumab (IGF-1 receptor Inhibitor), and rituximab or orbital decompression surgery/external orbital radiation. Close follow up is recommended as orbitopathy precedes hyperthyroidism in 20%of cases(3,4).References1-Kersten R. American Academy of Ophthalmology Section 7, Orbit, Eyelids and Lacrimal System 2004-2005: 48-56.2-Bahn RS. Graves’ ophthalmopathy. N Engl J Med 2010; 362: 726. 3-Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med 2020; 382: 341. 4-Zang S, Ponto KA, Kahaly GJ. Clinical review: Intravenous glucocorticoids for Graves’ orbitopathy: efficacy and morbidity. J Clin Endocrinol Metab 2011; 96: 320.Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.